The study deals with the genetic determinants of human and rodent neuroectodermal neoplasms utilizing physical chemical, molecular, cytochemical, chromosomal and electron microscopic techniques. The major emphasis of this research is to further define chromosome organization in normal and neoplastic cells. Two approaches are taken 1) the study of specific DNA sequences (with special emphasis on human DNA) and 2) the study of how these DNA sequences are arranged with respect to the higher order of chromosome structure. Basic studies on normal cells are undertaken in order to establish a reliable and quantitative framework for the definition of nuclear changes in malignant cells. We will continue to quantitatively analyze the number and types of satellite and other repeated DNAs, as well as unique, transcribed and translated DNAs in human glial neoplasms and in normal human cells in order to see if there are specific DNA components that are amplified or decreased in the course of malignant transformation. More detailed information on the relationship of several minor human satellite DNAs to each other and to complex repeating human DNA sequences will be analyzed using a variety of techniques. The relationship of isolated DNA fragments, representing several subsets of DNA, to the heterochromatic and euchromatic portions of the nucleus during different phases of the cell cycle, and in glial tumors where there is marked alteration in the DNA content of the nucleus, will further clarify organizational constraints of these DNAs. Chromosome structures and their three dimensional organization during interphase and metaphase will be studied under controlled conditions both in normal and tumor cells. Analysis of specific sequences, their localization in the nucleus, and their three dimensional organization will be used to further evaluate the hypothesis of DNA polyploidy and positional changes suggested by previous experiments.